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Antimicrobial Agents and Chemotherapy, January 1998, p. 23-27, Vol. 42, No. 1
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Efficacy of CS-834 against Experimental Pneumonia Caused by Penicillin-Susceptible and -Resistant Streptococcus pneumoniae in Mice

Takashi Fukuoka,1 Harumi Kawada,1 Akiko Kitayama,1 Tetsufumi Koga,1 Mikie Kubota,1 Tamako Harasaki,1 Yasuki Kamai,1 Satoshi Ohya,1,* Hiroshi Yasuda,1 Masayuki Iwata,1 and Shogo Kuwahara2

Biological Research Laboratories, Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140,1 and Department of Microbiology, School of Medicine, Toho University, Tokyo 143,2 Japan

Received 25 March 1997/Returned for modification 11 August 1997/Accepted 17 October 1997

The efficacy of CS-834, a novel oral carbapenem, was assessed by using a murine model of pneumonia caused by penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae and was compared with those of oral cephems, i.e., cefteram pivoxil, cefpodoxime proxetil, cefdinir, and cefditoren pivoxil. Intranasal inoculation of 106 CFU of penicillin-susceptible or penicillin-resistant S. pneumoniae in the exponential growth phase induced pneumonia and bacteremia in ddY mice within 48 h. For the treatment of infections caused by the penicillin-susceptible strain the antibiotics were administered orally at 0.4, 2, and 10 mg/kg of body weight twice daily for 2 days beginning at 24 h after bacterial inoculation, and for the treatment of infections caused by a penicillin-resistant strain the antibiotics were administered at 2, 10, and 50 mg/kg twice daily for 2 days beginning at 24 h after bacterial inoculation. Among the antibiotics tested, CS-834 exhibited the most potent efficacy against both types of strains. Against infections caused by penicillin-susceptible S. pneumoniae, CS-834 at all doses significantly reduced the numbers of viable cells in both the lungs and blood. Cefpodoxime proxetil at all doses and cefteram pivoxil and cefditoren pivoxil at doses of 2 and 10 mg/kg showed comparable efficacies. Against infections caused by penicillin-resistant S. pneumoniae, CS-834 at doses of 10 and 50 mg/kg showed the most potent efficacy among the antibiotics tested, resulting in the maximum decrease in the numbers of viable cells in the lungs. Comparable efficacies were observed with cefteram pivoxil and cefpodoxime proxetil at doses of 50 mg/kg each. The concentration of CS-834 in the lungs and blood was higher than that of cefdinir and was lower than those of the other antibiotics tested, suggesting that the potent therapeutic efficacy of CS-834 reflects its strong activity against S. pneumoniae.

* Corresponding author. Mailing address: Biological Research Laboratories, Sankyo Co., Ltd., 2-58 Hiromachi 1-chome, Shinagawa-ku, Tokyo, 140, Japan. Phone: 81-3-3492-3131. Fax: 81-3-5436-8565. E-mail: ohya{at}shina.sankyo.co.jp.

Antimicrobial Agents and Chemotherapy, January 1998, p. 23-27, Vol. 42, No. 1
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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